The Insulin Resistance and Atherosclerosis Study (IRAS) is a multicenter study of the relationship between insulin resistance and cardiovascular disease (CVD) and its risk factors in a tri-ethnic (African-American, Hispanic, and non-Hispanic white) population aged 40 to 69 years at baseline. The study population was selected to insure adequate numbers of participants within gender and glucose tolerance groups (normoglycemia, impaired tolerance, and non-insulin dependent diabetes mellitus [NIDDM]). IRAS is the first large epidemiologic study to include detailed measurements of insulin sensitivity and secretion. During the first four years of funding, the IRAS Investigators successfully designed and implemented the first phase of the study--a cross-sectional evaluation of 1,625 participants. The current proposal requests an additional five years of funding for the prospective follow-up and reexamination of the IRAS cohort. The requested funding period consists of three phases. During the first phase (Y05 and Y06), the investigators propose to conduct a substudy to address the measurement of insulin sensitivity in individuals with NIDDM. This substudy will evaluate several alternate techniques for measuring insulin sensitivity in approximately 115 non-IRAS volunteers with NIDDM. In addition, all IRAS participants will be contacted annually for incident cardiovascular and other major health events. During the second phase (Y07 and Y08), a follow-up examination of the IRAS cohort will be conducted with the goal of determining predictors of changes in insulin sensitivity, cardiovascular risk factors, measures of atherosclerosis development, and incident cardiovascular events. Additionally, throughout the first four years (Y05-Y08), there will be a continued major effort devoted to the analysis and reporting of the cross-sectional data from the first IRAS examination. The final phase (Y09) will include database closure and archival, and analysis and reporting of the longitudinal results.